The Inspire Bio-resource Research Platform for Healthy Aging INSPIRE Platform

1. Markers of aging: The identification of (a set of) markers of aging will be allowed from the constitution of a large dataset of clinical, para-clinical and digital data as well as a comprehensive biobank comprising: blood, saliva, urine, nasopharyngeal swabbing, skin material (swabbing, stripping, biopsies), dental plaque, feces, hair bulb.

In this part of the study, we will take advantage of three complimentary approaches to look for the best markers of aging: without a priori approach (omics: transcriptomics, proteomics, lipidomics); semi a priori approach (field-specific omic. I.e. metabolism, inflammation, cell cycle, mitochondrial network…); and targeted approach (pre-identified targets).

Icope app (developed in collaboration with W.H.O.) for smartphone and tablet to measure intrinsic capacity domains. This app will be used for the remote (at-distance) evaluation and monitoring (self-monitoring, monitoring by a caregiver, or a healthcare provider) of intrinsic capacity domains; for the monitoring, we will use only the Icope Step 1. When declines are detected in the Icope Step 1, we will use the Icope Step 2 (data collected by research nurses in a home visit or at the research facility) to confirm the decline and, then, look for the causes determining such declines.

Basic and instrumental activities of daily living (ADL). Basic ADLs will be assessed using the 6-item (eg, bathing, feeding, dressing) Katz scale; instrumental ADLs (IADL) will be assessed using the 8-item (eg, cooking, manipulating money) Lawton scale. These variables are measured as a clinical measurement of functional ability and, thus, healthy aging in late ages, according to WHO definition.

Mini-nutritional assessment (MNA) and food frequency questionnaire. Nutritional status will be evaluated using the MNA (see Vitality description in Icope Step 2). A short (12-item; the question on physical activity has been removed since already investigated using other assessment tools in this project) food frequency questionnaire will be used to assess dietary quality. Nutritional status and diet may affect both intrinsic capacity domains and potential biomarkers of aging.

. Lifestyle questionnaires:

1. Physical activity (PA) and sedentary time: Based on the International Physical Activity Questionnaire (IPAQ) long form.
2. Smoking: This will be evaluated by two questions: Do you currently smoke: any tobacco product? ; e-cigarettes? Responses will be anchored by the terms: daily; weekly, but not daily; less often than weekly; not at all.
3. Alcohol consumption: This will be evaluated by a question of the food frequency questionnaire
4. Solar exposure: Sun Protection and Exposure Habits Questionnaires

Objectively measured physical activity (PA) and sleep parameters. This will be assessed with an activPal activity monitor. Participants will wear the activPal for one week every two-years and will bring it back personally to the research facilities. Attention will be paid for participants wearing the activity monitor always during the same season to avoid bias related to seasonal changes. PA is one of the most important behaviors for healthy aging, being associated with both intrinsic capacity domains and biomarkers. Sleep changes are often associated with aging and may affect healthy aging.

Visceral pain. This will be assessed with a 4-item self-reported questionnaire. This questionnaire is particularly important for investigations on biomarkers from feces.

Patient reported outcome measures (PROM). Four PROMs, covering cognition and mobility (the two functions that largely determine disability and increased healthcare costs), the overall feeling of fatigue and social isolation. All of them are validated tools for cognition, we will use the Cognitive Function Instrument (CFI), a 14-item questionnaire with score varying from 0 to 14, higher is worse. All the other three PROMs come from the NIH-funded initiative "Patient-reported outcomes measurement information system"

Patient reported outcome measures (PROM). Four PROMs, covering cognition and mobility (the two functions that largely determine disability and increased healthcare costs), the overall feeling of fatigue and social isolation. All of them are validated tools for cognition, we will use the Cognitive Function Instrument (CFI), a 14-item questionnaire with score varying from 0 to 14, higher is worse. All the other three PROMs come from the NIH-funded initiative "Patient-reported outcomes measurement information system"

Patient reported outcome measures (PROM). Four PROMs, covering cognition and mobility (the two functions that largely determine disability and increased healthcare costs), the overall feeling of fatigue and social isolation. All of them are validated tools for cognition, we will use the Cognitive Function Instrument (CFI), a 14-item questionnaire with score varying from 0 to 14, higher is worse. All the other three PROMs come from the NIH-funded initiative "Patient-reported outcomes measurement information system"

Patient reported outcome measures (PROM). Four PROMs, covering cognition and mobility (the two functions that largely determine disability and increased healthcare costs), the overall feeling of fatigue and social isolation. All of them are validated tools for cognition, we will use the Cognitive Function Instrument (CFI), a 14-item questionnaire with score varying from 0 to 14, higher is worse. All the other three PROMs come from the NIH-funded initiative "Patient-reported outcomes measurement information system"

Patient reported outcome measures (PROM). Four PROMs, covering cognition and mobility (the two functions that largely determine disability and increased healthcare costs), the overall feeling of fatigue and social isolation. All of them are validated tools for cognition, we will use the Cognitive Function Instrument (CFI), a 14-item questionnaire with score varying from 0 to 14, higher is worse. All the other three PROMs come from the NIH-funded initiative "Patient-reported outcomes measurement information system"

Patient reported outcome measures (PROM). Four PROMs, covering cognition and mobility (the two functions that largely determine disability and increased healthcare costs), the overall feeling of fatigue and social isolation. All of them are validated tools for cognition, we will use the Cognitive Function Instrument (CFI), a 14-item questionnaire with score varying from 0 to 14, higher is worse. All the other three PROMs come from the NIH-funded initiative "Patient-reported outcomes measurement information system"

Oral Health Assessment Tool (OHAT) provides a global overview of oral health. It is composed of 8 items: lips, tongue, gum-mucosa, saliva, natural teeth, prostheses, oral hygiene and pain. Each item is scored 0, 1 or 2. A score of 0 indicates the absence of degradation, a score of 2 indicates a significant presence of degradation, a score of 1 indicates that there is a remarkable modification without a significant or widespread degradation. The minimum score is 0 (satisfactory oral status) and the maximum score is 16 (degraded oral status).

Short physical performance battery (SPPB) and 30-sec chair rise test. The SPPB will be evaluated. With the participants' consent, performance in the SPPB tests will be video-recorded using standard cameras placed in three different angles in the room: the images will be analyzed to look for digital markers of aging through the patterns of motor function and subsequent subjects risk-stratification. The number of chair rises within 30secwill also be assessed in a fraction of participants. These measurements provide clinical information about mobility.

The Mini-mental state examination (MMSE) and neuropsychological tests. The MMSE is a scale that provides total scores ranging from 0 to 30 (higher values represent better cognitive function). Besides the MMSE, in subjects less than 70 years-old the following neuropsychological tests will be used: free and total recall of the Free and Cued Selective Reminding Test, the Digit Symbol Substitution Test, score from the Wechsler Adult Intelligence Scale-Revised, and the Category Naming Test (2-minute category fluency in animals); when combined in a composite Z-score, these variables provide accurate information about participants' cognitive function.

The Mini-mental state examination (MMSE) and neuropsychological tests. The MMSE is a scale that provides total scores ranging from 0 to 30 (higher values represent better cognitive function). Besides the MMSE, in subjects less than 70 years-old the following neuropsychological tests will be used: free and total recall of the Free and Cued Selective Reminding Test, the Digit Symbol Substitution Test, score from the Wechsler Adult Intelligence Scale-Revised, and the Category Naming Test (2-minute category fluency in animals); when combined in a composite Z-score, these variables provide accurate information about participants' cognitive function.

Skin elasticity (cutometer measurement). This measures the bio-mechanical properties of the skin by applying mechanical stress to the skin. The measuring principle is based on suction and elongation. A device will be used to generate a negative pressure which can vary between 20 and 500 mbar. The area of the skin to be measured is drawn into the probe opening by this pressure. The depth of skin penetration inside the probe opening is determined by an optical measurement system. The stress can be exerted at different depths of the skin: the 2mm probe solicits the skin at the superficial dermis; the 6mm probe engages the skin more deeply, at the level of the deep dermis, at the limit of the hypodermis.

Whole body magnetic resonance to measure the Isokinetic muscle strength with Dual Energy X-ray absorptiometry (DEXA°

maximum oxygen consumption (VO²max) and aerobic power (blood sampling before and after the effort).